Fibromyalgia: New Hope and New Pharmaceuticals

While few therapies have proven effective in the past, recent pharmacologic advances provide new hope for this difficult-to-treat disorder.

By Andrew J. Holman, MD

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Fibromyalgia may produce pain ranging from mild to severe and is now among the major reasons for referral to a pain center. Until now, few therapies have proven effective but several new agents provide pain relief in most cases. This update reviews both the old and new pharmacologic agents used to treat fibromyalgia.

Despite the introduction of the term fibrositis in 1904 by Gower,1 progress in understanding FMS has been slow. However, recent innovative strategies and broader investigation of its cause, beyond a myopic focus on psychiatric or musculoskeletal research, have finally led to a new expectation of improved treatment outcome.

Firm confidence in a diagnosis is essential before formulating and implementing an effective treatment strategy in any medical condition. For many clinicians, the diagnosis of FMS remains confusing despite validated criteria published by the American College of Rheumatology in 1990 (See Table 1).2 While specific tenderness, or tender points, have been promoted as diagnostic evidence of this disorder, honest debate and, at times, unruly skepticism, is evident even among rheumatologists. While helpful as inclusion criteria for research studies, fibromyalgia tender-point intensity can still vary from day to day in clinical practice, leading to diagnostic uncertainty. Nevertheless, clinicians can readily recognize and attempt to treat the common presentation of chronic, unexplained, widespread pain, tenderness, and fatigue of fibromyalgia.

Table 1. The 1990 American College of Rheumatology Criteria for the Classification of Fibromyalgia2

History of Widespread Pain. Definition:

Pain is considered widespread when all of the following are present:

Pain in the left side of the body

Pain in the right side of the body

Pain above the waist

Pain below the waist

In addition, axial skeletal pain (cervical spine or anterior chest or thoracic spine or low back) must be present. In this definition, shoulder and buttock pan is considered as pain for each involved side. Low back pain is considered lower segment pain.

Pain in 11 of 18 Tender Point Sites on Digital Palpation. Definition:

Pain on digital palpation, must be present in at least 11 of the following 18 tender point sites:

Occiput: bilateral, at the suboccipital muscle insertion

Low cervical: bilateral, at the anterior aspects of the intertransverse spaces at C5-C7

Trapezius: bilateral, at the midpoint of the upper border

Supraspinatus: bilateral, at origins, above the scapula spine near the medial border

Second rib: bilateral, at the second costochondral junctions, just lateral to the junctions on upper surfaces

Lateral epicondyle: bilateral, 2 cm distal to the epicondyles

Gluteal: bilateral, in the upper outer quadrants of buttocks in anterior fold of muscle

Digital palpation should be performed with an approximate force of 4 kg. for tender point to be considered positive the subject must state that the palpation was painful. Tender is not to be considered painful.

Clinical Characteristics

Fibromyalgia syndrome (FMS) is a specific musculoskeletal condition affecting 10 million Americans validated by specific criteria published by the American College of Rheumatology in 1990.

Diagnosis is based on demonstration of widespread pain for at least 3 months and specific tenderness to gently palpation symmetrically at tender points.

FMS is not a diagnosis of exclusion and important comorbid pain can complicate the presentation and require independent diagnosis and treatment.

Pathogenesis

FMS symptoms have been reproduced after auditory fragmentation of stage III/IV sleep for 4 nights.

Similar experiments in athletes and disruption of rapid eye movement (REM) sleep did not lead to FMS symptoms.

Pain and tenderness have been attributed to amplified central pain processing, but the specific mechanism has not yet been identified.

Abnormal regulation of autonomic control is a prominent feature of FMS and may explain the strong association of irritable bowel syndrome, irritable bladder, palpations and vasomotor instability with FMS.

Inadequate hippocampal attenuation of autonomic arousal fragmenting sleep appears to be a fundamental feature of FMS.

Dopaminergic control of hippocampal function suggests a novel treatment approach to FMS.

Clinical Presentation

Almost 85% of FMS cases occur in women, but men are often undiagnosed. In fact, the divergent presentation of FMS in men compared with women has been well reported.15 Pain and muscular spasm are generally more diffuse and vague in men. It appears that the hallmark diagnostic finding in FMS, 11 of 18 specific tender points, becomes apparent to the clinician and male patients much later in its clinical course. Response rates (RRs) to a variety of pharmacologic options are also less robust in men. The cause of these gender differences in presentation and response is uncertain, but may relate to behavioral differences, comorbidities, or hormonal variations, including clinically amenable testosterone deficiency in men receiving chronic opioids.

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